Correction: Xiang, S., et al. Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells. Molecules 2014, 19, 13235-13250.

We would like to change the Affiliation addresses on Page 13235 of paper [1], [...].

Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway.

Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G0 /G1 arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.

miR-122 inhibits cancer cell malignancy by targeting PKM2 in gallbladder carcinoma.

Gallbladder cancer (GBC) is one of the lethal diseases of digestive system. Increasing evidence prompt that microRNAs (miRs) might provide a novel therapeutical target for malignant disease. The antitumor effect of miR-122 to GBC is worth to be investigated. miR-122 expression level in GBC tissue sample and cell lines were assayed by qRT-PCR. miR-122 mimics were transfected for upregulation of miR-122 expression. Cell function was assayed by CCK8, flow cytometry, wound healing assay, migration assay, and invasion assay. The target genes of miR-122 were predicated by TargetScan online program and verified by western blot and luciferase report gene assay. miR-122 was decreased in GBC tissue and cell lines. The exogenous introduction of miR-122 exhibits multiple antitumor effect in GBC cell proliferation, invasion, and metastasis. Further studies revealed that the PKM2 was a regulative target of miR-122 in GBC cell. miR-122 also inhibits TGF-ß-induced epithelium mesenchymal transformation of GBC cell by downregulating PKM2 expression. These findings suggest that miR-122 plays an important role in tumorigenesis of GBC through interfering PKM2, highlighting its usefulness as a potential therapeutic agent in GBC.

Evaluation of two inflammation-based prognostic scores in patients with resectable gallbladder carcinoma.

BACKGROUND: Survival after surgery for gallbladder cancer is generally poor. A number of inflammation-based prognostic scores have been established to help predict survival after surgery for several types of cancer. The objective of this study was to analyze and compare the utility of two inflammation-based prognostic scores, the Glasgow prognostic score (GPS) and the neutrophil-to-lymphocyte ratio (NLR), for predicting survival in patients with gallbladder cancer after surgery with curative intent. METHODS: We retrospectively reviewed the medical records of 85 patients with histologically confirmed, resectable gallbladder carcinoma (GBC), who were to receive curative surgery in our department. Univariate and multivariate analyses were performed to evaluate the relationship between the variables to overall survival (OS). RESULTS: A significant difference was detected in OS in patients with low and high GPS and NLR scores. Univariate analyses using clinicopathological characteristics revealed that tumor differentiation; tumor invasion; lymph node metastasis; tumor, node, metastasis classification system stage; positive margin status; combined common bile duct resection; serum levels of C-reactive protein, albumin, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and CA125; white blood cell count; and GPS and NLR were all associated with OS. Among these characteristics, multivariate analysis demonstrated that a high GPS was independently associated with poorer OS, together with tumor invasion, lymph node metastasis, and positive margin status. CONCLUSIONS: GPS is superior to NLR with respect to its prognostic value for patients with GBC after surgery with curative intent. GPS is not only associated with tumor progression but is also an independent marker of poor prognosis.

Bufalin induces cell cycle arrest and apoptosis in gallbladder carcinoma cells.

Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine Chan Su, has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro. However, no detailed studies have so far been reported on its action on human gallbladder carcinoma cells. In this study, bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (ΔΨm) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways. Intraperitoneal injection of bufalin for 3 weeks significantly inhibited the growth of gallbladder carcinoma (GBC-SD) xenografts in athymic nude mice. Taken together, the results indicate that bufalin may be a potential agent for the treatment of gallbladder cancer.

Oridonin induces apoptosis and cell cycle arrest of gallbladder cancer cells via the mitochondrial pathway.

BACKGROUND: Gallbladder cancer is the most frequent malignancy of the bile duct with high aggressive and extremely poor prognosis. The main objective of the paper was to investigate the inhibitory effects of oridonin, a diterpenoid isolated from Rabdosia rubescens, on gallbladder cancer both in vitro and in vivo and to explore the mechanisms underlying oridonin-induced apoptosis and cell cycle arrest. METHODS: The anti-tumor activity of oridonin on SGC996 and NOZ cells was assessed by the MTT and colony forming assays. Cell cycle changes were detected by flow cytometric analysis. Apoptosis was detected by annexin V/PI double-staining and Hoechst 33342 staining assays. Loss of mitochondrial membrane potential was observed by Rhodamine 123 staining. The in vivo efficacy of oridonin was evaluated using a NOZ xenograft model in athymic nude mice. The expression of cell cycle- and apoptosis-related proteins in vitro and in vivo was analyzed by western blot analysis. Activation of caspases (caspase-3, -8 and -9) was measured by caspases activity assay. RESULTS: Oridonin induced potent growth inhibition, S-phase arrest, apoptosis, and colony-forming inhibition in SGC996 and NOZ cells in a dose-dependent manner. Intraperitoneal injection of oridonin (5, 10, or 15 mg/kg) for 3 weeks significantly inhibited the growth of NOZ xenografts in athymic nude mice. We demonstrated that oridonin regulated cell cycle-related proteins in response to S-phase arrest by western blot analysis. In contrast, we observed inhibition of NF-κB nuclear translocation and an increase Bax/Bcl-2 ratio accompanied by activated caspase-3, caspase-9 and PARP-1 cleavage after treatment with oridonin, which indicate that the mitochondrial pathway is involved in oridonin-mediated apoptosis. CONCLUSIONS: Oridonin possesses potent anti-gallbladder cancer activities that correlate with regulation of the mitochondrial pathway, which is critical for apoptosis and S-phase arrest. Therefore, oridonin has potential as a novel anti-tumor therapy for the treatment of gallbladder cancer.

Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study.

BACKGROUND: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection. METHODS: We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration. RESULTS: The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen. CONCLUSIONS: Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.

Effects of oxymatrine on the apoptosis and proliferation of gallbladder cancer cells.

Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladder cancer cells (GBC-SD and SGC-996) were investigated using cell counting kit-8 and colony formation assays. Annexin V/propidium iodide double staining was performed to investigate whether OM could induce apoptosis in gallbladder cancer cells. The mitochondrial membrane potential (ΔΨm) and expression of apoptosis-associated proteins were evaluated to identify a mechanism for the effects of OM. In addition, the RNA expression of relevant genes was measured by qRT-PCR using the SYBR Green method. Finally, a subcutaneous implantation model was used to verify the effects of OM on tumor growth in vivo. We found that OM inhibited the proliferation of gallbladder cancer cells. In addition, Annexin V/propidium iodide double staining showed that OM induced apoptosis after 48 h and the ΔΨm decreased in a dose-dependent manner after OM treatment. Moreover, the activation of caspase-3 and Bax and downregulation of Bcl-2 and nuclear factor κB were observed in OM-treated cells. Finally, OM potently inhibited in-vivo tumor growth following subcutaneous inoculation of SGC-996 cells in nude mice. In conclusion, OM treatment reduced proliferation and induced apoptosis in gallbladder cancer cells, which suggests that this drug may serve as a novel candidate for adjuvant treatment in patients with gallbladder cancer.

Cordycepin induces S phase arrest and apoptosis in human gallbladder cancer cells.

Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells.

Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (ΔΨm) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-κB, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer.

Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis.

The aim of this current study was to investigate the clinicopathologic features and prognostic significance of UbcH10 in pancreatic ductal adenocarcinoma (PDA). Real-time quantitative RT-PCR was employed to examine UbcH10 expression in 20 pairs of PDA and adjacent non-cancerous tissues. In addition, UbcH10 expression was analyzed by immunohistochemistry in 94 clinicopathologically characterized PDA cases. The correlation of UbcH10 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of UbcH10 mRNA and protein in PDA tissues were both significantly higher than those in non-cancerous tissues. Simultaneously, high expression of UbcH10 was significantly correlated with the clinical stage (p<0.001), degree of histological differentiation (p<0.001), and lymph node metastasis (p=0.001). Moreover, high expression of UbcH10 was significantly associated with poor overall survival in PDA patients. In conclusion, UbcH10 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for PDA.

Prognostic significance of nemo-like kinase (NLK) expression in patients with gallbladder cancer.

Nemo-like kinase (NLK), a serine/threonine protein kinase, has been implicated in tumor development and progression, and plays an important role in diverse signaling pathways by phosphorylating a variety of transcription factors. Recent studies demonstrated that altered expression of NLK was observed in various types of human cancers. However, the clinical significance of NLK expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance of NLK in GBC, and found that nuclear NLK protein overexpression was frequently detected in GBC tissues. The overexpression of NLK was significantly correlated with histological grade, TNM stage, and perineural invasion. The results of Kaplan-Meier analysis indicated that a high expression level of NLK resulted in a significantly poorer prognosis of GBC patients (P = 0.002). Furthermore, multivariate Cox regression analysis showed that high NLK expression was an independent prognostic factor for GBC patients (HR = 3.077). In conclusion, overexpression of NLK is closely related to progression of GBC, and NLK could be used as a potential prognostic marker for GBC patients.

Isolated complete caudate lobectomy for hepatic tumor of the anterior transhepatic approach: surgical approaches and perioperative outcomes.

BACKGROUND: How to resect the caudate lobe safely is a major challenge to current liver surgery which requires further study. METHODS: Nine cases (6 hepatic cell carcinoma, 2 cavernous hemangioma and 1 intrahepatic cholangiocacinoma) were performed using the anterior transhepatic approach in the isolated complete caudate lobe resection. During the operation, we used the following techniques: the intraoperative routine use of Peng's multifunction operative dissector (PMOD), inflow and outflow of hepatic blood control, low central venous pressure and selective use of liver hanging maneuver. RESULTS: There were no perioperative deaths observed after the operation. The median operating time was 230 ± 43.6 minutes, the median intraoperative blood loss was 606.6 ± 266.3 ml and the median length of postoperative hospital stay was 12.6 ± 2.9 days. The incidence of complications was 22.22% (2/9). CONCLUSION: PMOD and "curettage and aspiration" technique can be of great help of in the dissection of vessels and parenchyma, clearly making caudate lobe resection safer, easier and faster.

[The role of preoperative TACE on hepatocellular carcinoma located in caudate lobe].

OBJECTIVE: To evaluate the effect of preoperative transarterial chemoembolization (TACE) on hepatocellular carcinoma located in caudate lobe. METHODS: Totally 29 cases of caudate lobe hepatocellular carcinoma admitted from January 2001 to December 2010 were analyzed retrospectively. Among the 29 patients, 23 were male and the other 6 were female. The median age was 52 years. According to receiving preoperative TACE or not, the 29 cases were divided into two groups: preoperative TACE plus surgery (group A, n = 11) and surgery only (group B, n = 18). The surgical results and long-term survival were compared between two groups. RESULTS: After TACE, the diameter of the tumour reduced by over 33.3% in 3 patients, 10.0% to 33.3% in 6 patients, and less than 10.0% in 2 patients. The duration of surgery and intraoperative blood loss in group A were (298 ± 39) minutes and (1031 ± 310) ml, respectively. The duration of surgery and intraoperative blood loss in group B were (281 ± 54) minutes and (868 ± 403) ml, respectively. No significant difference was found in terms of these two groups (t = 1.006, P = 0.324; t = 1.223, P = 0.232). In addition, 6 cases in group A developed complications and 4 cases in group B did so. Only one patient died because of postoperative complication, and this patient belonged to group A. No significant difference was found between two groups (χ(2) = 0.028, P = 0.868; χ(2) = 0.633, P = 0.426). The 5-year survival rate was 56.8% in group A and 34.9% in group B. The difference did not reach significant difference (P = 0.132). CONCLUSIONS: For hepatocellular carcinoma located in caudate lobe, preoperative TACE does not significantly increase the surgical difficulty and impair the safety. In addition, preoperative TACE has the tendency to provide benefit to long-term survival.

Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/ß-Catenin and Akt/NF-κB signaling pathways.

BACKGROUND: Surgical resection combined with radiotherapy and chemotherapy remains a common clinical treatment for glioblastoma multiforme (GBM). However, the therapeutic outcomes have not been satisfying due to drug resistance and other factors. Quercetin, a phytoingredient capable of crossing the blood-brain barrier, has shown effectiveness in the treatment of various solid tumors. Nevertheless, the potential of quercetin in GBM treatment has not been adequately explored. PURPOSE: This study aims to investigate the effects and mechanisms of quercetin on MGMT+GBM cells. METHODS: The potential targets and mechanisms of quercetin in glioma treatment were predicted based on network pharmacology and molecular docking. The effects of quercetin on cell inhibition rate, cell migration ability, cell cycle arrest, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Mitochondrial superoxide formation and apoptosis were measured by the CCK8 assay, wound healing assay, PI/RNase staining, JC-1 assay, DCFH-DA assay, MitoSOX staining and Annexin V-FITC/PI double staining, respectively. The methylation status of the MGMT promoter was assessed through methylation-specific polymerase chain reaction (MS-PCR). DNA damage was quantified by alkaline/neutral comet assay and TUNEL assay. The intracellular localization and expression of NF-κB and MGMT were revealed by immunofluorescence. The expression of migration-related proteins, matrix metalloproteinases, apoptosis-related proteins, cyclins, DNA damage/repair enzymes and related pathway proteins was detected by Western blot. RESULTS: Network pharmacology identified 96 targets and potential molecular mechanisms of quercetin in glioma treatment. Subsequent experiments confirmed the synergistic effect of quercetin in combination with temozolomide (TMZ) on T98G cells. Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle. The collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process of quercetin-induced apoptosis. In addition, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), γH2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression. Quercetin may influence the expression of the key DNA repair enzyme, MGMT, by dual suppression of the Wnt3a/ß-Catenin and the Akt/NF-κB signaling pathways, thereby promoting apoptosis. Inhibition of Wnt3a and Akt using specific inhibitors hindered MGMT expression. CONCLUSION: Our study provides the first evidence that quercetin may induce apoptosis in MGMT+GBM cells via dual inhibition of the Wnt3a/ß-Catenin pathway and the Akt/NF-κB signaling pathway. These findings suggest that quercetin could be a novel agent for improving GBM treatment, especially in TMZ-resistant GBM with high MGMT expression.

DNA methylation of RUNX3 promotes the progression of gallbladder cancer through repressing SLC7A11-mediated ferroptosis.

Gallbladder cancer (GBC) is a type of rare but highly aggressive cancer with a dismal prognosis. Runt-related transcription factor 3 (RUNX3), a member of the runt-domain family, and its promoter methylation have been widely observed in a variety of human malignancies. However, the biological function and underlying mechanism of RUNX3 in GBC remain elusive. In this study, bisulfate sequencing PCR (BSP), Western blot, and qPCR were applied to identify the expression level and DNA methylation level of RUNX3 in GBC tissues and cells. The transcriptional relationship between RUNX3 and Inhibitor of growth 1 (ING1) was validated by dual-luciferase reporter assay and ChIP assay. A series of gain-of-function and loss-of-function assays were performed to detect the function and the regulatory relationship of RUNX3 in vitro and in vivo. RUNX3 was aberrantly downregulated in GBC cells and tissues caused by DNA Methyltransferase 1 (DNMT1)-mediated methylation, and downregulation of RUNX3 is associated with poor prognosis of GBC patients. Functional experiments reveal that RUNX3 can induce ferroptosis of GBC cells in vitro and in vivo. Mechanistically, RUNX3 induces ferroptosis by activating ING1 transcription, thereby repressing SLC7A11 in a p53-dependent manner. In conclusion, the downregulation of RUNX3 is mediated by DNA methylation, which promotes the pathogenesis of gallbladder cancer through attenuating SLC7A11-mediated ferroptosis. This study gives novel insights into the role of RUNX3 in the ferroptosis of GBC cells, which may contribute to developing potential treatment targets for GBC.

NLK is a key regulator of proliferation and migration in gallbladder carcinoma cells.

Gallbladder cancer (GBC) is one of the most lethal neoplasm and is the fifth most common malignancy of gastrointestinal tract. The prognosis of gallbladder cancer is extremely terrible partially due to metastasis. Thus, understanding the molecular pathways controlling metastasis of this lethal disease may provide new targets for targeted therapeutic approach. In this study, we investigated the function of nemo-like kinase (NLK) in GBC growth and migration. Lentivirus-mediated siRNA was employed to alleviate the expression level of NLK in GBC cell lines (GBC-SD and SGC-996). Real-time PCR and western-blot analysis demonstrated that both mRNA and protein levels of NLK in GBC-SD and SGC-996 cells were decreased after infection with NLK-siRNA-expressing lentivirus (Lv-shNLK). The proliferation and in vitro tumorigenesis (colony formation) ability as well as migration of GBC-SD and SGC-996 cells with low NLK expression decreased significantly. Our results suggested that NLK is a key regulator involved in proliferation and migration of GBC, and it could be used as a potential therapeutic target for GBC.

Primary closure versus T-tube drainage in laparoscopic common bile duct exploration: a meta-analysis of randomized clinical trials.

PURPOSE: To compare the safety and effectiveness of primary closure with those of T-tube drainage in laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis. METHODS: A comprehensive search was performed in the PubMed, EmBase, and Cochrane Library databases. Only randomized controlled trials comparing primary closure with T-tube drainage in LCBDE were considered eligible for this meta-analysis. The analyzed outcome variables included postoperative mortality, overall morbidity, biliary complication rate, biliary leak rate, reoperation, operating time, postoperative hospital stay, time to abdominal drain removal, and retained stone. All calculations and statistical tests were performed using ReviewerManager 5.1.2 software. RESULTS: A total of 295 patients (148 patients with primary closure and 147 patients with T-tube drainage) from three trials were identified and analyzed. No deaths occurred in any of the trials. Primary closure showed significantly better results in terms of morbidity (risk ratio (RR), 0.51; 95% confidence interval (CI), 0.30 to 0.88), biliary complication without a combination of retained stone (RR, 0.44; 95% CI, 0.20 to 0.97), reoperation (RR, 0.16; 95% CI, 0.03 to 0.87), operating time (mean difference (MD), -20.72; 95% CI, -29.59 to -11.85), postoperative hospital stay (MD, -3.24; 95% CI, -3.96 to -2.52), and time to abdominal drainage removal (MD, -0.45; 95% CI, -0.86 to -0.04). Statistically significant differences were not found between the two methods in terms of biliary leak, biliary complication, and retained stones. CONCLUSION: The current meta-analysis indicates that primary closure of the common bile duct is safer and more effective than T-tube drainage for LCBDE. Therefore, we do not recommend routine performance of T-tube drainage in LCBDE.

Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation.

The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer. However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear. After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells. Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc). Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer. In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect. Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future.